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Doppler ultrasound when used appropriately is an invaluable tool in monitoring high risk twin pregnancy. There are no recent multicentre randomised controlled trials examining the value of routine umbilical artery doppler (UA), middle cerebral artery doppler (MCA), cerebroplacental ratio (CPR), uterine artery doppler (UtA) and ductus venosus doppler in uncomplicated twins. Thus, there is lack of international consensus in relation to incorporation of doppler ultrasound in the routine surveillance of uncomplicated multiples. In this chapter we will discuss how twins differ from singletons in their growth trajectories and progression of doppler abnormalities. International clinical guidelines are reviewed. Recommendations for doppler surveillance (routine or selective) with reference to recent studies are made.

Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP.This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests.The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain.In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Abnormal uterine artery Doppler (UtAD) studies early in gestation have been associated with adverse pregnancy outcomes. However, their association with complications in the third trimester is weak. We aim to review the prediction ability for perinatal complications of these indices in the third trimester.Abnormal UtAD waveforms in the third trimester are associated with preeclampsia, small-for-gestational age infants (SGA), preterm birth, perinatal death, and other perinatal complications, such as cesarean section for fetal distress, 5 min low Apgar score, low umbilical artery pH, and neonatal admission to the ICU, particularly in SGA infants. UtAD prediction performance is improved by the addition of maternal characteristics as well as biochemical markers to prediction models and is more precise if the evaluation is made closer to delivery or diagnosis.This review shows that the prediction accuracy of UtAD for adverse pregnancy outcomes during the third trimester is moderate at best. UtAD have limited additive value to prediction models that include PlGF and sFlt-1. Serial assessments rather than a single third trimester evaluation may enhance the prediction performance of the UtAD combined models.

Growth hormone (GH) is secreted by cells in the anterior pituitary on two time scales: discrete pulses over minutes that occur within a 24-hr pattern. Secretion reflects the balance of stimulatory and inhibitory inputs from the hypothalamus and is influenced by gonadal steroids, stress, nutrition, and sleep/wake states. We propose a novel approach for the analysis of GH data and use this approach to quantify (i) the timing, amplitude and the number of GH pulses and (ii) GH infusion, clearance and basal secretion (i.e., time invariant) rates, using serum GH sampled every 10 minutes during an 8-hour sleep study in 18 adolescents. In our method, we approximate hormonal secretory events by deconvolving GH data via a two-step coordinate descent approach. The first step utilizes a sparse-recovery approach to estimate the timing and amplitude of GH secretory events. The second step estimates physiological parameters. Our method identifies the timing and amplitude of GH pulses and system parameters from experimental and simulated data, with a median R^2 of 0.93, among experimental data. Recovering GH pulses and model parameters using this approach may improve the quantification of GH parameters under different physiological and pathological conditions and the design and monitoring of interventions.

The hypoglossal canal (HC) is an unusual location of the posterior fossa dural arteriovenous fistula (AVF), which usually occurs in the transverse or sigmoid sinus. Herein, we report a case of HC dural AVF successfully treated with transvenous coil embolization using detachable coils in a 68-year-old woman who presented with headache and left pulsatile tinnitus for 2 months. Brain magnetic resonance imaging (MRI) and cerebral angiography revealed left HC dural AVF. The pulsatile bruit disappeared immediately after the procedure. Follow-up MRI showed complete disappearance of the fistula. Precise localization of the fistula through careful consideration of the anatomy and transvenous coil embolization using a detachable coil can facilitate the treatment for HC dural AVF.

Preterm birth (PTB) is a major public health problem worldwide. It can occur spontaneously or be medically indicated for obstetric complications, such as pre-eclampsia (PE) or fetal growth restriction. The main objective of this study was to investigate whether there is a shared uteroplacental etiology in the first trimester of pregnancy across PTB subtypes.This was a retrospective cohort study of singleton pregnancies that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, between March 2018 and December 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm, which includes maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and pregnancy-associated plasma protein-A (PAPP-A). Women with a risk of ≥ 1 in 50 for preterm PE were classified as high risk and offered prophylactic aspirin (150 mg once a day) and serial ultrasound assessments. The following delivery outcomes were evaluated: PTB 37 weeks, iatrogenic PTB (iPTB) and spontaneous PTB (sPTB). Logistic regression analyses were performed to assess the association of PTB, iPTB and sPTB with an increased risk of preterm PE. A model for prediction of PTB 37 weeks and 33 weeks was developed and its performance was compared with that of an existing model in the literature.A total of 11 437 women were included in the study, of whom 475 (4.2%) had PTB. Of these, 308 (64.8%) were sPTB and 167 (35.2%) were iPTB. Patients with PTB had a higher body mass index, were more likely to be of black or Asian ethnicity, be smokers, have pregestational hypertension or diabetes, or have a history of previous PTB. They also had higher MAP (87.7 vs 86.0 mmHg, P 0.0001), higher UtA-PI multiples of the median (MoM) (0.99 vs 0.92, P 0.0001) and lower PAPP-A MoM (0.89 vs 1.08, P 0.0001) compared to women with a term birth. In women at high risk of PE, the odds ratio for iPTB was 6.0 (95% CI, 4.29-8.43; P 0.0001) and that for sPTB was 2.0 (95% CI, 1.46-2.86; P 0.0001). A prediction model for PTB 37 weeks and 33 weeks, developed based on this cohort, included previous PTB, black ethnicity, chronic hypertension, diabetes mellitus, PAPP-A MoM and UtA-PI MoM. The performance of the model was similar to that of an existing first-trimester prediction model for PTB 33 weeks (area under the curve, 0.704 (95% CI, 0.653-0.754) vs 0.694 (95% CI, 0.643-0.746)).Increased first-trimester risk for uteroplacental dysfunction was associated with both iPTB and sPTB, implying a shared etiological pathway. The same factors used to predict PE risk show acceptable discrimination to predict PTB at 33 weeks. Women at high risk of uteroplacental dysfunction may warrant additional monitoring and management for an increased risk of sPTB. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND A correlation between atypical recurrences and minimally-invasive surgery has been suggested in case of urothelial cancer; however, very few data are available on the role of pneumo peritoneum in terms of gas flow and intra-abdominal pressure. The objective of the study is to analyze the impact of CO2 pneumoperitoneum variation on an inert material as surrogate of neoplastic cells. MATERIAL AND METHODS We designed an experimental model mimicking pneumoperitoneum in three settings: sealed flow (no leakage), pulsatile flow (alternating efflux and influx) and continuous flow (AirSeal® insufflator). Each experiment was characterized by a pre-determined gas flow and pressure, trocar distance and position from the particles. Hounsfield density (HD) variation in the areas of interest was measured as index of graphite powder dispersion. A Linear regression model was employed to measure the correlation between modifiable variables and HD. RESULTS HD was lower in the pulsatile compared to both the sealed and continuous flows (p 0.05). CONCLUSIONS Flow and pressure setting, in-flow trocar distance and contiguity from the tumor, and pneumoperitoneum stability may be all crucial component in minimally invasive surgery. In vivo, these variables should be considered as potential risk factors for tumor cells spread within the abdominal cavity.

Many complications in physiology are associated with a deviation in flow in arteries due to a stenosis. The presence of stenosis may transition the flow to weak turbulence. The degree of stenosis as well as its configuration whether symmetric or non-symmetric to the parent artery influences whether the flow would stay laminar or transition to turbulence. Plenty of research efforts focus on investigating the role of varying degrees of stenosis in the onset of turbulence under steady and pulsatile flow conditions. None of the studies, however, have focused on investigating this under oscillatory flow conditions as flow reversal is a major occurrence in a number of physiologic flows, and is of particular relevance in cerebrospinal fluid flow research. Following up on the previous work in which a $$75\%$$ 75 % stenosis was studied, this contribution is a detailed investigation of the role of degrees of stenosis on transition in an oscillatory flow. A cylindrical pipe with $$25\%$$ 25 % , $$50\%$$ 50 % and $$60\%$$ 60 % reductions in area in axisymmetric and eccentric configurations is studied for transition with 3 different pulsation frequencies of a purely oscillatory flow. Cycle averaged Reynolds numbers between 1800 and 2100 in steps of 100 are studied for each configuration resulting in 72 simulations each conducted on 76,800 CPU cores of a modern supercomputer. It is found that a higher degree of stenosis and eccentricity causes earlier transition to turbulence in oscillatory flow. The results further demonstrate that a higher frequency of oscillation results in larger hydrodynamic instability in the flow, which is more prominent in smaller degrees of stenosis.

The patient is a 50-year-old male with a history of tobacco use presented for evaluation of pulsatile right-hand mass. The patient was employed as a barber but had no known history of trauma or injury. He was diagnosed with hypothenar hammer syndrome and underwent excision of ulnar artery aneurysm with reconstruction of ulnar artery with interposition saphenous vein graft. The presented case describes an uncommon presentation of hypothenar hammer syndrome in a patient without history of repetitive blunt trauma or injury and discusses the diagnosis, pathophysiology and treatment options for symptomatic ulnar artery aneurysm.

Background: Hypertension alters the structure and function of cerebral blood vessels, and is an important risk factor for stroke and cerebral small vessel disease (cSVD). However, the pathophysiological process is not yet well understood. This study aimed to investigate the relationship between the pulsatility measures in small perforating arteries and hypertension, since hypertension-induced arterial stiffening may lead to a higher blood flow pulsatility and lower damping. Methods: We examined 28 patients with essential hypertension and 25 age- and sex-matched healthy controls (mean age: 63.4, range: 43–81 years, 26 males). Blood flow velocity waveforms were acquired in the lenticulostriate arteries (LSAs) and the middle cerebral artery using phase-contrast MRI at 7 Tesla. Several cSVD markers were scored. The velocity and pulsatility measures were compared between the hypertensives and controls. Results: A higher pulsatility index (PI) in the LSAs and a lower damping factor (DF) was found in the hypertensive compared to the normotensive group ( P =0.015, P =0.015, respectively), but no association was found for the PI in the middle cerebral artery. Higher systolic and mean arterial pressures were associated with higher PI in the LSA and DF. For diastolic blood pressure, only an association with a lower DF was found. Adjusting for cSVD score did not alter these relationships. Conclusions: This study shows a higher PI in the LSAs and a lower DF in subjects with hypertension, independent of cSVD presence. This supports the hypothesis that hypertension-induced arterial remodeling may alter the intracerebral blood flow velocity profiles, which could eventually contribute to cerebral tissue damage. Registration: URL: https://trialsearch.who.int/ ; Unique identifier: NL7537 and NL8798

Introduction: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. Methods: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. Results: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. Conclusions: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.

Mechanical heart valves (MHV) and its fluid dynamics inside a pulsatile pediatric ventricular assist device (PVAD) can be associated with blood degradation. In this article, flow structures are analyzed and compared by an experimental investigation on the effect of bileaflet MHV positioned at varying angles in the inlet port orifice of a PVAD.Time-resolved particle image velocimetry was applied to characterize the internal flow of the device. St Jude Medical bileaftlet valves were used on the inlet orifice and positioned at 0°, 15°, 30°, 45°, 60°, and 90° in relation to the centerline of the device. Three planes with bidimensional velocity magnitude fields were considered in the analysis with visualization of diastolic jets, device wall washing patterns and flow circulation during emptying or systole of the pump. Also, the washing vortex area, and vertical velocity probabilities of regurgitant flows in the inlet valve were evaluated.The results show that a variation in the angle of the MHV at the inlet port produced distinct velocities, fluid structures, and regurgitant flow probabilities within the device. MHV positioned at an angle of 0° generated the strongest inlet jet, larger vortex area during filling, more prominent outgoing flow, and less regurgitation compared to the angles studied. The presence of unfavorable fluid structures, such as small vortices, and/or sudden flow structure interruption, and/or regurgitation, were identified at 45° and 90° angles.The 0° inlet angle had better outcomes than other angles due to its consistency in the multiple parameters analyzed.

Durable continuous-flow left ventricular assist devices (cfLVADs) demonstrate superior survival, cardiac functional status, and overall quality of life compared to medical therapy alone in advanced heart failure. Previous studies have not considered the impact arterial compliance may have on pump performance or developed arterial pressure. This study assessed the impact of alterations in arterial compliance, preload, and afterload on continuous-flow pump function and measured hemodynamics using an in-vitro pulsatile mock circulatory loop. Decreased arterial compliance was associated with a significant increase in arterial pressure pulsatility which was not evident in the flow pulsatility, as displayed in pump flow waveforms. There were marked changes in the pump flow waveforms due to the significant alteration in the aortoventricular gradient during diastole according to the changes in compliance. This study demonstrates that changes in systemic blood pressure, afterload, and left ventricular contractility each significantly affects the flow waveform. The association of hypertension with lower aortic compliance results in markedly decreased diastolic flow rates which may be important in contributing to a greater risk of adverse events under cfLVAD support.

Aortic stiffness increases with advancing age, more than doubling during the human life span, and is a robust predictor of cardiovascular disease (CVD) clinical events independent of traditional risk factors. The aorta increases in diameter and length to accommodate growing body size and cardiac output in youth, but in middle and older age the aorta continues to remodel to a larger diameter, thinning the pool of permanent elastin fibers, increasing intramural wall stress and resulting in the transfer of load bearing onto stiffer collagen fibers. Whereas aortic stiffening in early middle age may be a compensatory mechanism to normalize intramural wall stress and therefore theoretically “good” early in the life span, the negative clinical consequences of accelerated aortic stiffening beyond middle age far outweigh any earlier physiological benefit. Indeed, aortic stiffness and the loss of the “windkessel effect” with advancing age result in elevated pulsatile pressure and flow in downstream microvasculature that is associated with subclinical damage to high-flow, low-resistance organs such as brain, kidney, retina, and heart. The mechanisms of aortic stiffness include alterations in extracellular matrix proteins (collagen deposition, elastin fragmentation), increased arterial tone (oxidative stress and inflammation-related reduced vasodilators and augmented vasoconstrictors; enhanced sympathetic activity), arterial calcification, vascular smooth muscle cell stiffness, and extracellular matrix glycosaminoglycans. Given the rapidly aging population of the United States, aortic stiffening will likely contribute to substantial CVD burden over the next 2–3 decades unless new therapeutic targets and interventions are identified to prevent the potential avalanche of clinical sequelae related to age-related aortic stiffness.

The objective of this study was to evaluate a measure of the responsiveness and reliability of the pulse volume recording upstroke ratio (PVRr). A database of 389 subjects undergoing lower extremity revascularization was analyzed. Subjects were included in the analysis if they had undergone pedal radiographs, had PVRs performed pre- and postlower extremity revascularization, and had regular pulsatile digital waveforms with a pressure recording on both PVRs. The responsiveness of the PVRr was assessed by means of the postoperative percent change in comparison to the digital pressures. A statistically significant negative correlation was observed (Pearson -0.421; p = .007) indicating that as digital pressures increased, the PVRr decreased. Further, measurement of the reliability of the PVRr was performed on a selection of 10 recordings by 2 residents and 3 board-certified surgeons. The observed intraclass correlation coefficient of measurements was 0.960. Results of this investigation provide evidence in support of the responsiveness and inter-rater reliability in the calculation of the pulse volume recording upstroke ratio.

A comprehensive computational study is performed to investigate the effectiveness of vortex generators (VGs) applied to mechanical bi-leaflet heart valves. Co-rotating and counter-rotating VG configurations are compared to a control valve without VGs. Detailed flow fields are obtained and used to elucidate the underlying flow physics. It was found that VGs reduce flow separation over the leaflets and hence reduce the Reynolds shear stress (RSS) in the vicinity regions of heart valve. The co-rotating VG configuration demonstrates a better performance compared with the counter-rotating configuration in terms of the RSS, turbulent kinetic energy production and velocity distributions, especially in the peripheral jet flows. The fraction of blood damage in the co-rotating configuration shows a 4.7% reduction in comparison to the control case, while a 3.7% increase is observed in the counter-rotating configuration. The passive flow control technique of applying co-rotating VG illustrates a great potential to help mitigate the hemodynamic factors leading to potential blood damage risk.

First, to compare the ophthalmic artery peak systolic velocity (PSV) ratio at 35-37 weeks' gestation among women who delivered small-for-gestational-age (SGA) or growth-restricted (FGR) neonates in the absence of hypertensive disorders, women who developed pre-eclampsia (PE) or gestational hypertension (GH) and those without SGA, FGR, PE or GH. Second, to examine the association of PSV ratio with placental growth factor (PlGF) and mean arterial pressure (MAP). Third, to assess the associations of PSV ratio, PlGF and MAP with birth-weight Z-score and percentile.This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, first (PSV1) and second (PSV2) peaks of systolic velocity, MAP and serum PlGF. The values of PSV ratio, MAP and PlGF were converted to multiples of the median (MoM) or delta values, and the median MoM or delta of these variables in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, PlGF MoM and MAP MoM with birth-weight Z-score after exclusion of PE and GH cases. Regression analysis was also used to examine the association of PSV ratio delta with logThe study population included 2287 pregnancies, of which 1954 (85.4%) were not affected by FGR, SGA, PE or GH, 49 (2.1%) were complicated by FGR in the absence of PE or GH, 160 (7.0%) had SGA in the absence of FGR, PE or GH, 60 (2.6%) had PE and 64 (2.8%) had GH. Compared with unaffected pregnancies, in both the FGR and SGA groups, the means of PSV ratio delta (0.042 (95% CI, 0.007-0.076) and 0.032 (95% CI, 0.016-0.049), respectively) and MAP MoM (1.028 (95% CI, 1.006-1.050) and 1.048 (95% CI, 1.035-1.060), respectively) were increased, while the mean of PlGF MoM was decreased (0.495 (95% CI, 0.393-0.622) and 0.648 (95% CI, 0.562-0.747), respectively). However, the magnitude of these changes was smaller than in the PE and GH groups. Ophthalmic artery waveform analysis revealed that the predominant feature of pregnancies complicated by SGA in the absence of hypertensive disorders was a reduction in PSV1, whereas, in those with hypertensive disorders, there was an increase in PSV2. In non-hypertensive pregnancies, there were linear inverse associations of PSV ratio delta and MAP MoM with birth-weight Z-score, with increased values in small neonates and decreased values in large neonates. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small neonates and high PlGF levels in large neonates. There was a significant correlation of ophthalmic artery PSV ratio delta with both logAssuming that the ophthalmic artery PSV ratio is a reflection of the interplay between cardiac output and peripheral vascular resistance, the linear association between PSV ratio and birth-weight Z-score in non-hypertensive pregnancies suggests the presence of a continuous physiological relationship between fetal size and cardiovascular response rather than a dichotomous relationship between high peripheral resistance and low cardiac output in small compared with non-small fetuses. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Objective: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. Design: Prospective cohort. Setting: Kagadi Hospital, Uganda. Population: Non-anomalous singleton pregnancies. Methods: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. Main outcome measures: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. Results: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09–21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18–11.88). Conclusion: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. Tweetable abstract: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

Although mechanical circulatory support saved many lives during the last decade, clinical observations have shown that the continuous flow pumps are associated with a much higher incidence of gastrointestinal bleeding and kidney problems, among others, compared with the earlier generation pulsatile pumps. However, the presence of several moving mechanical components made pulsatile pumps less durable, bulky, and prone to malfunction, ultimately leading to bias in favor of continuous flow designs.The aim of the current work is to create a prototype tubular pulsatile pump and to test the timing of the pump in a left heart simulator.A left heart simulator to mimic pumping from a failing heart was created. This was used to experimentally test the output of a prototype ventricular assist device relative to a failing heart in the form of flow and pressure. The effect of pulsation timing was quantified.A failing heart was simulated with an average flow rate of 1.1 L/min and a systolic pressure of 47 mm Hg. With the pump, the flow rate increases to 4.8 L/min and a systolic pressure of 110 mm Hg, in a copulsation mode, while activating for 300-400 ms. If the activation time is reduced, or increased, the pump becomes less effective. Load on the heart is reduced when the pump operates in a counterpulsation mode.A pulsatile pump, like the one proposed, provides adequate output for mechanical circulatory support, while minimizing the number of moving parts that could otherwise lead to tribological wear.

Background. The impairment of microcirculation is associated with the unfavorable outcome for extracorporeal membrane oxygenation (ECMO) patients. Studies revealed that pulsatile modification improves hemodynamics and attenuates inflammation during ECMO support. However, whether flow pattern impacts microcirculation and endothelial integrity is rarely documented. The objective of this work was to explore how pulsatility affects microcirculation during ECMO. Methods. Canine animal models with cardiac arrest were supported by ECMO, with the i-Cor system used to generate nonpulsatile or pulsatile flow. The sublingual microcirculation parameters were examined using the CytoCam microscope system. The expression of hsa_circ_0007367, a circular RNA, was measured during ECMO support. In vitro validation was performed in pulmonary vascular endothelial cells (PMVECs) exposed to pulsatile or nonpulsatile flow, and the expressions of hsa_circ_0007367, endothelial tight junction markers, endothelial adhesive molecules, endothelial nitric oxide synthases (eNOS), and NF-κB signaling activity were analyzed. Results. The pulsatile modification of ECMO enhanced microcirculatory perfusion, attenuated pulmonary inflammation, and stabilized endothelial integrity in animal models; meanwhile, the expression of hsa_circ_0007367 was significantly upregulated both in animals and PMVECs exposed to pulsatile flow. In particular, upregulation of hsa_circ_0007367 stabilized the expressions of endothelial tight junction markers zonula occludens- (ZO-) 1 and occludin, followed by modulating the endothelial nitric oxide synthases (eNOS) activity and inhibiting the NF-κB signaling pathway. Conclusion. The modification of pulsatility contributes to microcirculatory perfusion and endothelial integrity during ECMO. The expression of hsa_circ_0007367 plays a pivotal role in this protective mechanism.

Arterial stenosis is a significant cardiovascular disease requiring accurate estimation of the pressure gradients for determining hemodynamic significance. In this paper, we propose Generalized Bernoulli Equation (GBE) utilizing interpolated-based method to estimate relative pressures using streamlines and pathlines from 4D Flow MRI.4D Flow MRI data in a stenotic phantom model and computational fluid dynamics simulated velocities generated under identical flow conditions were processed by Generalized Bernoulli Equation (GBE), Reduced Bernoulli Equations (RBE), as well as the Simple Bernoulli Equation (SBE) which is clinically prevalent. Pressures derived from 4D flow MRI and noise corrupted CFD velocities were compared with pressures generated directly with CFD as well as pressures obtained using Millar catheters under identical flow conditions.It was found that SBE and RBE methods underestimated the relative pressure for lower flow rates while overestimating the relative pressure at higher flow rates. Specifically, compared to the reference pressure, SBE underestimated the maximum relative pressure by 22[Formula: see text] for a pulsatile flow data with peak flow rate [Formula: see text] and overestimated by around 40[Formula: see text] when [Formula: see text]. In contrast, for GBE method the relative pressure values were overestimated by 15[Formula: see text] with [Formula: see text]and around 10[Formula: see text] with [Formula: see text].GBE methods showed robust performance to additive image noise compared to other methods. Our findings indicate that GBE pressure estimation over pathlines attains the highest level of accuracy compared to GBE over streamlines, and the SBE and RBE methods.

Cerebro-placental ratio (CPR) is a doppler tool contributes to clinical decision-making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM-complicated-pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA.This prospective single-center cohort study included non-anomalous singleton pregnancies in women with GDM. Those with pre-pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR-defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5-minute Apgar7, cord arterial pH 7.0, hypoxic ischemic encephalopathy, or NICU admission24 hours.Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0-37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16-31] versus 60th [IQR 31-82]; P = .002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P = .68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2-8.3).In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia.

The maternal vasculature undergoes tremendous growth and remodeling (GR) that enables a 15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the maternal hemodynamics is necessary to improve prognosis. The goal of this paper is to develop a mathematical framework to characterize maternal vascular GR and hemodynamics in uncomplicated human pregnancies. A validated 1D model of the human vascular tree from the literature was adapted and inlet blood flow waveforms at the ascending aorta at 4 week increments from 0 to 40 weeks of gestation were prescribed. Peripheral resistances of each terminal vessel were adjusted to achieve target flow rates and mean arterial pressure at each gestational age. Vessel growth was governed by wall shear stress (and axial lengthening in uterine vessels), and changes in vessel distensibility were related to vessel growth. Uterine artery velocity waveforms generated from this model closely resembled ultrasound results from the literature. The literature UA-PI values changed significantly across gestation, increasing in the first month of gestation, then dramatically decreasing from 4 to 20 weeks. Our results captured well the time-course of vessel geometry, material properties, and UA-PI. This 1D fluid-GR model captured the salient hemodynamic features across a broad range of clinical reports and across gestation for uncomplicated human pregnancy. While results capture available data well, this study highlights significant gaps in available data required to better understand vascular remodeling in pregnancy.

Pulmonary artery aneurysms (PAAs) are rare, but clinically important because their rupture can cause sudden death. We present the first case of an asymptomatic patient with an unruptured PAA that was successfully diagnosed by dynamic digital chest radiography (DDCR) and was treated surgically. DDCR is a state-of-the-art temporally resolved radiographic technique that offers high-quality fluoroscopy-like images at a low radiation dose. Although noncontrast chest computed tomography (CT) revealed only a nonspecific nodule, DDCR delineated this lesion as a pulsatile nodule synchronized with cardiac pulsations, establishing the diagnosis of PAA. This diagnosis was confirmed by CT pulmonary angiography and surgery.

Background The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. Methods A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. Results The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. Conclusions Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.

Objective To assess the degree of correlation/agreement of maternal-fetal Doppler parameters between normal and growth-restricted fetuses (fetal growth restriction [FGR]). Methods The present observational and retrospective study included 274 singleton pregnancies. The following maternal-fetal Doppler parameters were assessed: uterine artery (UAt), umbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), and umbilical-cerebral ratio (U/C). The assessment of FGR was based on the Figueiras and Gratacós9 criteria. Spearman correlation coefficients were estimated to assess the correlation between resistance (RI) and pulsatility (PI) indices of Doppler parameters. The agreement between two Doppler parameters was assessed by the Kappa coefficient. Results In total, 502 Doppler examinations were included, and FGR was observed in 19 out of 274 fetuses. A strong correlation was observed between RI and PI of UAt, UA, and MCA in all of the samples (p1.0 and CPR1,0 e RCp

OBJECTIVE Catheter manometry is used frequently in neuroendovascular surgery for assessing cerebrovascular pathology. The accuracy of pressure data with different catheter setups requires further validation. METHODS In a silicone human vascular model with a pulsatile pump, pressure measurements were taken through multiple arrangements of 2 guide catheters and 6 microcatheters. The systolic pressure, diastolic pressure, mean pressure, pulse pressure, and area under the curve of the waveform were recorded through catheters with controls at arterial blood pressure ranges. Linear regression modeling was performed, correlating transduction area and relative pulse pressure. Thresholds for acceptable accuracy were ≥ 90%. RESULTS Mean pressure demonstrated < 4% variation between all 24 catheter setups and respective controls. A strong linear correlation (r2 = 0.843, p < 0.0005) between microcatheter transduction area and relative pulse pressure with a threshold of 0.50 mm2 was seen (i.e., 0.031-inch inner diameter [ID]). For guide catheters with indwelling microcatheters, there was also a strong linear correlation (r2 = 0.840, p < 0.0005) of transduction area to pulse pressure. The guide catheters with obstructing microcatheters required a transduction area over fourfold higher compared with unobstructed microcatheters (2.21 mm2 vs 0.50 mm2). CONCLUSIONS Mean pressure measurements are accurate through microcatheters as small as 0.013-inch ID. Pulse pressure and waveform morphology may require a microcatheter ≥ 0.031-inch ID to achieve 90% accuracy, although the 0.027-inch ID microcatheter reached 85% accuracy. A 0.070-inch guide catheter with a microcatheter ≤ 0.042-inch outer diameter (e.g., Marksman 0.027-inch ID or smaller) allows accurate transduction of pulse pressure. Further validation of these benchtop findings is necessary before application in a clinical setting.

The objective of the present study was formulation and evaluation of pulsatile release tablets of Atenolol. A tablet system consisting of cores which was coated with layers of swelling and rupturable coatings. Cores containing Atenolol as model drug were prepared by direct compression with appropriate ratios of lactose and microcrystalline cellulose and then coated sequentially with different ratios of an inner swelling layer containing HPMC and an outer rupturable layer of Ethyl Cellulose. The effect of level of swelling layer and rupturable coating was investigated. The different formulation press coated by using different weight ratios of Hydroxy Propyl Methyl Cellulose (HPMC) / Ethyl Cellulose (EC) / both HPMC and EC. The optimum result was achieved in formulation containing HPMC: EC weight ratios. The F3 batch achieved a highest burst release after the lag time which is applicable pulsatile drug delivery system of Atenolol.

The importance of experimental setups able to reproduce cardiac functions was well established in the field of clinical innovations. The mock circulatory loops acquired rising relevance, and the possibility to have a complete reproduction of different and specific fluid dynamic conditions within the setup is pivotal. A system with enough versatility to reproduce the physiologic range of both flows and pressures is required. This study describes the design of a versatile setup composed by a custom pulsatile left ventricular pump system and a 3D-printed mock circulatory loop for the in vitro analysis of a patient-specific case of an aortic complex. The performances of the pump were validated first with a set of test flow profiles. It was demonstrated that the system was able to cover a wide range of aortic and mitral flows. Second, the pump system was inserted within the full mock circulatory loop. A patient-specific case was reproduced, both in terms of flow and pressure profiles. A successful validation of the flow and pressure waveforms was obtained by using patient-specific in vivo data from magnetic resonance analysis.

The lymphatic vascular function is regulated by pulsatile shear stresses through signaling mediated by intracellular calcium [Ca(2+)](i). Further, the intracellular calcium dynamics mediates signaling between lymphatic endothelial cells (LECs) and muscle cells (LMCs), including the lymphatic tone and contractility. Although calcium signaling has been characterized on LEC monolayers under uniform or step changes in shear stress, these dynamics have not been revealed in LMCs under physiologically-relevant co-culture conditions with LECs or under pulsatile flow. In this study, a cylindrical organ-on-chip platform of the lymphatic vessel (Lymphangion-Chip) consisting of a lumen formed with axially-aligned LECs co-cultured with transversally wrapped layers of LMCs was exposed to step changes or pulsatile shear stress, as often experienced in vivo physiologically or pathologically. Through real-time analysis of intracellular calcium [Ca(2+)](i) release, the device reveals the pulsatile shear-dependent biological coupling between LECs and LMCs. Upon step shear, both cell types undergo a relatively rapid rise in [Ca(2+)](i) followed by a gradual decay. Importantly, under pulsatile flow, analysis of the calcium signal also reveals a secondary sinusoid within the LECs and LMCs that is very close to the flow frequency. Finally, LMCs directly influence the LEC calcium dynamics both under step changes in shear and under pulsatile flow, demonstrating a coupling of LEC-LMC signaling. In conclusion, the Lymphangion-Chip is able to illustrate that intracellular calcium [Ca(2+)](i) in lymphatic vascular cells is dependent on pulsatile shear rate and therefore, serves as an analytical biomarker of mechanotransduction within LECs and LMCs, and functional consequences.

The retropharyngeal carotid artery (RCA) is a relatively rare anatomical malposition, and positional changes in the RCA is also extremely rare. In addition, there are some reports of ''wandering carotid artery'' which means that the carotid artery reciprocate positional changes (wandering) between its normal position and retropharyngeal regions, during follow-up evaluations. A male patient in his 50s with a chief complaint of globus pharyngeus. A pulsatile swelling of the posterior pharyngeal wall of the right side was found on clinical examination. In this case, the right carotid artery showed the clinical course of a wandering carotid artery, which reciprocated between its normal position and the retropharyngeal space during three serial MR investigations. Interestingly, both the most recent MR study and the MR study performed 4 years ago showed that the carotid artery at the level of the hyoid bone moved laterally (positional normalization) during the single MR investigation. This is a first case which showed a rare clinical course of a wandering carotid artery on serial follow-up MR studies and positional changes of carotid artery within a single MR study. It is important for clinicians to be aware of these phenomena, in order to avoid fatal and unexpected complications during clinical procedures.

To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset.The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept.The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%).Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

3D cine phase-contrast (4D flow) MRI is a sequence with great potential for non-invasive time-resolved 3D flowmetry at arbitrary vessel sections in various blood vessels. However, it is not widely known that the flowmetry with 4D flow MRI is vulnerable to pulsatile and non-uniform flow. Due to the limited spatial and temporal resolutions, averaging within the 3D voxel is occurring during the flowmetry. A simple solution is to avoid setting the measurement plane in the area where non-uniform flow is dominant, which is possible with an aid of streamline depictions generated by computational fluid dynamics (CFD) or 4D flow MRI data. Unlike 4D flow MRI, flowmetry in CFD simulation can use higher spatial and temporal resolution depending on computer performance; therefore, it is robust to fluctuating non-uniform flow. However, the performance of CFD simulations might be limited due to inlet conditions with low temporal resolution. Difficulty applying complex blood flow such as reflection flow from periphery may also limit accurate simulation. Caution should be taken when comparing the result of CFD simulation to that of 4D flow measurement.

Material treatment in pulsation reactors (PR) brings the possibility of synthesizing powdery products with advantageous properties, such as nanoparticle sizes and high specific surface areas, at an industrial scale. The extraordinary material properties can be ascribed to special process parameters in a PR, primarily the periodically varying conditions and the consequently enhanced heat and mass transfer between the medium and the particles of the material. Understanding the connections between the PR operation parameters, such as fuel and air intake or PR geometry, and the resulting process parameters (temperature distribution, flow velocity and pressure field, and frequency of the pulsations) is essential to enabling a controllable treatment process. Despite the long history of pulsation reactor technology, many connections and dependencies remain unclear. Thus, the influence of the fuel (and air) supply on the pulsation reactor behavior is experimentally examined in this study. The investigated PR characteristics and process parameters are primarily those that have an impact on the heat and mass transfer, i.e., the temperature distribution, flow velocity, and pressure field, and frequency of the pulsations. In addition to these, the harmonic distortion of the oscillations and the heat losses are evaluated.

The primary aim of this study was to investigate the potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on maternal and foetal Doppler findings. Doppler ultrasound findings were compared in 40 pregnant women diagnosed with COVID-19 disease who required hospitalisation (group 1) and 30 healthy pregnant women (group 2). Maternal characteristics and birth histories were recorded. Body mass index, gestational week at birth, type of delivery, oligihydroamnios, pre-term birth (37 weeks), low birth weight (10 percentile), perinatal death and f1st and 5th minute Apgar scores were recorded. Birth weights and foetal biophysical profile (BPP) scores in group 1 were significantly lower than those in group 2. There was a statistically significant between-group difference in the umbilical artery pulsatility index (PI), umbilical artery resistive index (RI), middle cerebral artery (MCA) PI, MCA RI, mean uterine artery (UtA) PI, mean UtA RI and cerebroplacental ratio (CPR), the parameters used to evaluate foetal-maternal blood flow. In the pregnant group diagnosed with COVID-19 and hospitalised, all foetal-maternal Doppler indicators of foetal-maternal blood flow were impaired, and birth weights and BPP scores in these patients were statistically significantly lower than those in the healthy controls.Impact statement

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

Mechanical circulatory support (MCS) devices are increasingly used as a treatment option in resuscitation or in patients with cardiogenic shock (CS). Prophylactic implantation in high-risk percutaneous coronary interventions (HRPCI) is another upcoming indication. The i-cor ECG-synchronized cardiac assist device combines the hemodynamic support of a veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with the ability to generate a pulsatile flow and thus decreasing adverse effects of VA-ECMO on myocardial function. Aim of this study was to obtain data concerning feasibility, safety and outcomes in both indications.A total of 47 patients (34 HRPCI, 13 CS) were included in nine German centers and participated in this study. Demographic and clinical parameters, procedural as well as follow-up data were prospectively recorded and analyzed.Device implantation and initiation of ECG-synchronized cardiac assist was technical successful in all cases and no failures of the consoles or disposable parts were observed. Furthermore, intended percutaneous coronary interventions and successful weaning from cardiac assist was achieved in 97.1% of HRPCI patients. We observed a 30d-survival of 94.1% in the HRPCI group and 69.2% in the CS group. Main complications in both groups were bleeding events (14.7% HRPCI, 23.1% CS) and critical limb ischemia (2.9% HRPCI, 38.5% CS).The i-cor ECG-synchronized cardiac assist device appears safe and feasible showing clinical outcomes comparable to existing data in the setting of high-risk percutaneous coronary interventions and acute cardiogenic shock. Further prospective trials are warranted to identify optimal patient and interventional characteristics that will benefit most of this novel kind of mechanical circulatory support.

Background The present study aims to compare regional oxygen supply determined by Near-Infrared Spectroscopy in the course of pulsatile perfusion with non-pulsatile perfusion during cardiopulmonary bypass in patients undergoing valvular heart surgery. Methods In this prospective randomized single-blinded trial, we enrolled adult subjects aged 18–65 years scheduled for elective valvular heart repair/replacement surgery with non-stenotic carotid arteries, employing a consecutive sampling method. Eligible patients were then randomly assigned in a 1:1 ratio to pulsatile or non-pulsatile perfusion during aortic cross-clamp. The primary outcome was regional cerebral oxygenation monitored by Near-Infrared Spectroscopy in each group. Results Seventy patients were randomly assigned, and each group comprised 35 patients. Mean age was 46.8 and 46.5 years in pulsatile and non-pulsatile groups, respectively. There were no significant between-group differences in regional cerebral oxygen saturation at different time points of cardiopulmonary bypass ( p-value for analysis of variance repeated measures: 0.923 and 0.223 for left and right hemispheres, respectively). Moreover, no significant differences in regional cerebral oxygen saturation levels from baseline between pulsatile and non-pulsatile groups at all desired time points for the left ( p = 0.51) and right ( p = 0.22) hemispheres of the brain were detected. Conclusion Pulsatile perfusion during cardiopulmonary bypass does not offer superior regional cerebral oxygenation measured by Near-Infrared Spectroscopy than non-pulsatile perfusion during cardiopulmonary bypass. Nonetheless, the efficacy of pulsatile flow in the subgroup of patients in whom cerebral blood flow is impaired due to carotid artery stenosis needs to be explored and evaluated by this method in future studies.

Objectives To analyze umbilical artery (UA) Doppler velocimetry and its possible role in placenta-mediated fetal growth restriction (FGR) in second- and third-trimester fetuses with trisomy 18 and 13. Methods UA pulsatility index (PI) and half-peak systolic velocity deceleration time (hPSV-DT) were measured in fetuses with trisomy 18 and 13. Correlation with gestational age, birthweight, and perinatal outcome was analyzed. Results A total of 80 measurements were taken from 33 fetuses with trisomy 18 and 19 with trisomy 13. Overall, there was a high prevalence of abnormal UA Doppler velocimetry. In fetuses with trisomy 18, 54% (27/50) of the UA PI values and 58% (29/50) of the UA hPSV-DT values were abnormal. In fetuses with trisomy 13, 80% (24/30) of the UA PI values and 87% (26/30) of the UA hPSV-DT values were abnormal. The prevalence of abnormal UA Doppler velocimetry increased with gestational age in both types of aneuploidy. However, this trend was only significant for trisomy 13 (p Conclusions A high prevalence of abnormal UA Doppler velocimetry was found in second- and third-trimester fetuses with trisomy 18 and 13, which further increased with gestational age. These results may well correlate with alterations described previously in the placenta, suggesting placental insufficiency has an important role in the development of FGR in these autosomal aneuploid fetuses.

The aim of this study was to evaluate flow dynamics in the aortic sinus and the neosinus (NS) after transcatheter heart valve (THV) implantation in valve-in-valve (ViV).Leaflet thrombosis may occur on THVs and affect performance and durability. Differences in flow dynamics may affect the risk for leaflet thrombosis.Hemodynamic assessment following THV implantation in a surgical aortic valve was performed in a left heart simulator under pulsatile physiological conditions. Assessment was performed using a 23-mm polymeric surgical aortic valve (not diseased) and multiple THV platforms, including self-expanding devices (26-mm Evolut, 23-mm Allegra, small ACURATE neo) and a balloon-expandable device (23-mm SAPIEN 3). Particle image velocimetry was performed to assess flow in the sinus and NS. Sinus and NS washout, shear stress, and velocity were calculated.Sinus and NS washout was fastest and approximately 1 cardiac cycle for each with the Evolut, ACURATE neo, and Allegra compared with the SAPIEN 3, with washout in 2 and 3 cardiac cycles, respectively. The Allegra showed the largest shear stress distribution in the sinus, followed by the SAPIEN 3. In the NS, all 4 valves showed equal likelihoods of occurrence of shear stress 1 Pa, but the Allegra showed the highest likelihoods of occurrence for shear stress1 Pa. The velocities in the sinus and NS were 0.05, 0.078, 0.080, and 0.075 m/s for Evolut, SAPIEN 3, ACURATE neo, and Allegra ViV, respectively.Sinus and NS flow dynamics differ substantially among THVs after ViV. Self-expanding supra-annular valves seem to have faster washouts compared with an equivalent-size balloon-expandable THV.

Our objective was to create a bio-engineered pump (BEP) for subpulmonary Fontan circulation support capable of luminal endothelialization and producing a 2-6 mmHg pressure gradient across the device without flow obstruction. To accomplish this, porcine urinary bladder submucosa was decellularized to produce a urinary bladder matrix (UBM) which produced acellular sheets of UBM. The UBM was cultured with human umbilical vein endothelial cells producing a nearly confluent monolayer of cells with the maintenance of typical histologic features demonstrating UBM to be a suitable substrate for endothelial cells. A lamination process created bilayer UBM sheets which were formed into biologic reservoirs. BEPs were constructed by securing the biologic reservoir between inlet and outlet valves and compressed with a polyurethane balloon. BEP function was evaluated in a simple flow loop representative of a modified subpulmonary Fontan circulation. A BEP with a 92-mL biologic reservoir operating at 60 cycles per minute produced pulsatile downstream flows without flow obstruction and generated a favorable pressure gradient across the device, maintaining upstream pressure of 6 mm Hg and producing downstream pressure of 13 mm Hg. The BEP represents potential long-term assistance for the Fontan circulation to relieve venous hypertension, provide pulsatile pulmonary blood flow and maintain cardiac preload.

Objectives To evaluate, in pregnancies complicated by hypertensive disorders of pregnancy (HDP), the predictive role of uterine artery (UtA) Doppler for pregnancy outcome compared to the definition of preeclampsia (PE) established by ISSHP recommendations. Study design Retrospective cohort study including singleton pregnancies diagnosed with HDP, who underwent UtA Doppler assessment at admission in 2011–2017. The study population was classified considering the presence or absence of PE and according to the presence or absence of abnormal UtA Doppler (mean pulsatility index > 95th percentile). Main outcome measures Pregnancy outcome, maternal and fetal complications, evaluated as composite outcomes (CO), and duration of pregnancy (from admission to delivery). Results A total of 311 mother-infant couples was included. The diagnostic ability of the two classifications was analysed comparing the relative likelihood ratio in the Biggerstaff graph. ISSHP definition turned out to be more efficient in detecting maternal adverse CO in comparison to UtA Doppler, relative positive likelihood ratio 1.50 (1.35–1.66) and 1.31 (1.07–1.60). UtA Doppler classification resulted more efficient in predicting adverse neonatal CO than PE definition, relative positive likelihood ratio 2.21 (1.77–2.75) and 1.61 (1.37–1.90). UtA Doppler was significantly associated with delivery at earlier gestational ages both for patients affected by PE and for women affected by HDP without superimposed PE (respectively p = 0.009 and p = 0.037). Conclusions UtA Doppler at HDP diagnosis is a useful bedside marker of fetal/neonatal complications, and is associated with pregnancy duration.

Patients with bilateral high degree carotid stenosis or occlusion impose high risk for neurological complications during coronary arterial bypass surgery (CABG). Former articles have described successful CABG in patients with bilateral carotid artery occlusion with uneventful recovery, with perioperative cerebral blood flow (CBF) monitoring consisting of EEG or near-infrared spectroscopy (NIRS). In this case report we describe use of pulsatile flow on cardiopulmonary bypass (CPB) and transcranial doppler (TCD) monitoring during a successful CABG in a patient with bilateral carotid occlusion, which led to a safe approach where changes in CBF were seen and analyzed with no lag between event and monitoring. Patients with previous CVA/TIA in the presence of carotid disease requiring coronary arterial bypass surgery (CABG) are associated with a higher risk of neurological ischemic event.

Surgical removal of tumor is the primary treatment of choice for glomus tympanicum (GT). However, because the tumor has abundant blood flow, bleeding control is crucial, and preoperative embolization may be performed. Here, we report the case of a 46-year-old female who visited our hospital with a complaint of right pulsatile tinnitus. A red pulsatile mass was found in the right tympanic cavity, and she was diagnosed with class B1 GT and subsequently underwent surgical treatment. We judged that bleeding could be controlled by intratympanic cavity manipulation alone and decided to perform transmeatal tumor resection without preoperative arterial embolization. After creating a tympanomeatal flap and performing an atticotomy, some pieces of Spongel(®) were inserted between the tumor and the tympanic wall. The Spongel(®) absorbed the blood and created a space between the tumor and tympanic wall, which allowed for the insertion of the tip of the Vesalius(®) handpiece to coagulate the tumor. The coagulation caused the tumor to shrink, thereby widening the space and allowing for further resection. Although the surgical manipulation caused bleeding, complete resection was achieved by the application of Spongel(®) and coagulation with Vesalius(®). Since the tip of the Vesalius(®) was not burned, hemostasis was successfully achieved, and the operation proceeded while maintaining a clear field of view. There was little bleeding and no postoperative complications. The patient was discharged on the sixth postoperative day. One year after surgery, pure tone audiometry showed no change in the level of bone conduction. Spongel(®) and Vesalius(®) are useful tools that allow to safely perform surgeries even in narrow spaces such as the tympanic cavity.

This study presents electrical modelling of the arterial system to understand the effect of adrenaline on the aortae and small arteries in terms of their resistance and compliance. There is no categorical documentation in the current literature on the precise locations of arterial resistance (R) and compliance (C) in vasculature. Knowledge of their exact locations in the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-to-beat changes in R and C in response to these drugs. Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressures were recorded before and after addition of adrenaline. Equivalent electrical models were simulated, and biological data was compared against the electrical equivalents to derive interpretations. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (P = .018); but the mean pressure remained the same (P = .357). Whereas in small artery, vasoconstriction caused an increase in systolic, diastolic, and mean pressures (P = .028). Simulations allow us to infer that vasoconstriction in the aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to alter the mean aortic pressure. Whereas vasoconstriction in small arteries increases resistance, but a decrease in compliance, if any, does not affect any of the pressure parameters measured. The presented study is first of its kind to give experimental evidence that large arteries and aorta are the only compliance vessels and small arteries are the only resistance vessels.

BACKGROUND The VentriFlo® True Pulse Pump (VentriFlo, Inc, Pelham, NH, USA) is a new pulsatile blood pump intended for use during short-term circulatory support. The purpose of this study was to evaluate the feasibility of the VentriFlo and compare it to a conventional centrifugal pump (ROTAFLOW, Getinge, Gothenberg, Sweden) in acute pig experiments. METHODS Pigs (40-45 kg) were supported by cardiopulmonary bypass (CPB) with the VentriFlo (n = 9) or ROTAFLOW (n = 5) for 6 h. Both VentriFlo and ROTAFLOW circuits utilized standard CPB components. We evaluated hemodynamics, blood chemistry, gas analysis, plasma hemoglobin, and microcirculation at the groin skin with computer-assisted video microscopy (Optilia, Sollentuna, Sweden). RESULTS Pigs were successfully supported by CPB for 6 h without any pump-related complications in either group. The VentriFlo delivered an average stroke volume of 29.2 ± 4.8 ml. VentriFlo delivered significantly higher pulse pressure (29.1 ± 7.2 mm Hg vs. 4.4 ± 7.0 mm Hg, p

OBJECTIVES To assess the impact of marginal (MCI) or velamentous (VCI) cord insertion on uterine artery pulsatility index (UtA PI), preeclampsia (PE), and offspring's birthweight (BW). METHODS A retrospective cohort study of singleton pregnancies, undergoing routine anomaly scan at 20+0 -23+6 gestational weeks, was conducted between 2016 and 2020. The effect of placental cord insertion on BW and UtA mean PI z-scores was assessed using the t test or analysis of variance and post-hoc tests; their association with PE was evaluated with the chi-square test. A multivariate logistic regression model was employed to assess the independent association of placental cord insertion and UtA PI z-score with PE, BW

The relative accuracy of pulsatile photoplethysmography applications (PPG) or handheld (HH) devices compared with the gold standard 12-lead electrocardiogram (ECG) for the diagnosis of atrial fibrillation is unknown.Digital databases were searched to identify relevant articles. Raw data were pooled using a bivariate model to calculate diagnostic accuracy measures and estimate Hierarchical Summary Receiver Operating Characteristic (HSROC).A total of 10 articles comprising 4296 patients (mean age 68.9 years, with 56% males) were included in the analysis. Compared with EKG, the pooled sensitivity of PPG and HH devices in AF detection was 0.93 (95% CI 0.87-0.96; p 0.05) and 0.87 (95% CI. 0.74-0.94; p 0.05), respectively. The pooled specificity of PPG and HH devices in AF detection was 0.91 (95% CI 0.88-0.94; p 0.05) and 0.96 (95% CI 0.90-0.98; p 0.05), respectively. The diagnostic odds ratio was 129 and 144 for PPG and HH devices, respectively. Fagan's nomogram showed the probability of a patient having AF and normal rhythm on PPG or HH devices was 2-3%, while the post-test probability of having AF with an irregular R-R interval on PPG or HH devices was 73% and 82%, respectively. The scatter plot of positive and negative likelihood ratio showed high confirmation of AF and reliability of exclusion of absence of irregular R-R intervals (positive likelihood ratio 10, and negative likelihood ratio 0.1) on HH devices while PPG was used as confirmation only.The PPG or HH devices can serve as a reliable alternative for the detection of AF.

Objective: This study is to formulate Nebivolol into a Pulsatile liquid, solid composite compression coated tablet, which will delay the release of the drug in early morning hypertension conditions. Methods: The liquid, solid composite tablet was formulated and compressed with the ethylcellulose coating polymer. The percent in vitro drug release of the liquid solid composite compressed tablet was tested. Based on disintegration time and wetting time, the LCS2, LCS3, LSC6, LCS7 and LCS12 formulations were found to be the optimized solid-liquid compacts fast-dissolving core tablet formulations, which may be excellent candidates for further coating with polymer to transfer into press coated pulsatile tablet formulations. Coating the core tablet with varying ethyl cellulose concentrations resulted in five different formulations of the pulsatile press-coated tablet (CT1, CT2, CT3, CT4, CT5). In vitro drug release, in vitro release, kinetic studies, in vivo pharmacokinetic and stability tests were all performed for the prepared pulsatile press coated tablet. Results: CT3 tablets are coated with ethyl cellulose polymer, which shows maximum controlled drug release from the core tablet i.e. 96.34±1.2% at 8th h. It shows there was an efficient delay in drug release form core tablet i.e. up to 3 h, followed by the maximum amount of drug release of 96.34±2.4 at 8h. Which shows the core drug will be more efficiently protected from the gastric acid environment 1.2 pH, duodenal environment 4.0 pH and release drug only in the small intestine. Conclusion: According to the findings, CT3 Pulsatile press-coated tablet increased the bioavailability of Nebivolol by 3.11 percent.